Epstein, J.B., Silverman, S., Paggiarino, D.A., Crockett, S., Schubert, M.M., Senzer, N.N., … Leveque, F.G. (2001). Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: Results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer, 92, 875–885.

Participants were randomized to receive either benzydamine HCl oral rinse, containing 0.15% benzydamine oral rinse (1.5 mg/ml benzydamine) or placebo, which identical in appearance and taste consisting of the vehicle only (approximately 10% alcohol by volume, menthol, peppermint oil, clove oil, and other flavoring agents).

Patients were to rinse with 15 ml of solution for two minutes, 4–8 times daily, before and during radiation therapy (RT) and for two weeks after completion of RT. If burning or stinging occurred, dilution of the rinse with water at 1:1 or 1:2 was allowed.  

Patients were evaluated before RT, twice weekly during RT, at the end of RT, and 2–3 weeks after RT.

• The sample consisted of 172 patients, with 84 receiving benzydamine and 88 receiving placebo.
• Patients ranged in age from 18–80 years old.
• Patients had been diagnosed with head and neck cancer and were scheduled to receive at least 5000 cGy RT via megavoltage treatment. Patients were eligible if at least two oral sites were included in RT.
• Patients were excluded if they had Karnofsky performance status of less than 80%, known hypersensitivity to benzydamine or typical nonsterioidal anti-inflammatory drugs, had residual oral or pharyngeal mucositis from previous RT or chemotherapy, or were already on RT and had taken experimental drugs within 30 days of study start.

The study was conducted at 16 centers in North America (15 in the United States and 1 in Canada).

• Mucositis assessment involved evaluating 14 anatomic areas for erythema, pseudomembrane, and ulceration using a 4-point scale ranging from 0–3.
• Pain in the mouth or throat and pain during meals was assessed on a 7-point categorical self-rating scale ranging from 0–6.

Benzydamine produced a 26.3% reduction in mean mucositis area under the curve (AUC) compared with placebo for overall 0–5000 cGy (p = 0.009).

Pain also decreased as evidenced by a delay in use of concomitant systemic analgesics. Mouth pain showed a 25.8% reduction in AUC (p = 0.064) versus placebo, and throat pain showed a 22.5% reduction in AUC (p = 0.064).

Pain during meals was not effectively reduced.

Benzydamine was not effective in reducing more severe mucositis in patients receiving high, single, daily RT regimens of 220 cGy per day or more.

• The study is limited because of the small sample size.
• The intervention is not approved by the U.S. Food and Drug Administration.
• The decrease in pain was not statistically significant.